Infectious agents have been associated with the new disease, Acquired Immunodeficiency Syndrome (AIDS), but it is not yet known whether their role is primary or secondary in the disease. The primary factor in AIDS may be a new or mutated virus, but it is also possible that common endemic organism(s) can produce severe disease of this form in immunosuppressed or otherwise susceptible individuals. In either case, it is important to investigate factors which predispose high risk individuals to this disease. Work performed by us and others over the past 10 years has shown that several components of semen are highly immunosuppressive and have strong effects on a variety of immune functions both in vitro and in vivo. Most AIDS victims are homosexual men with a history of exposure to semen in highly vascularized sites, and recent studies have shown that many healthy homosexual men have suppressed immunologic reactivity. One possibility is that semen factors induce immunosuppression in this group and predispose them to AIDS. In the proposed research project we will use the mouse experimental model to study the effects of oral, rectal and intraperitoneal administration of semen or semen components on various immunologic parameters and tissues. 1. We will use characterized mouse lymphocyte subpopulation markers to determine if population shifts occur in lymphoid tissues or the circulation. 2. We will use in vitro tests of lymphocyte function (lymphocyte transformation, Jerne plaque, natural killer cell and cytotoxicity assays) to determine if specific immunologic activities are impaired. 3. We will test for resistance to transplantable tumors and record the appearance of any spontaneous tumors. 4. We will measure antibody levels and use immunogluorescence and Western Blot techniques to determine the antigenic specificity of antibodies unique to sementreated animals. 5. We will histologically examine the mucosal surfaces in sites of semen administration to determine if the protective barrier to infectious organisms is disrupted. Our objectives are to (1) establish an animal model for studies on AIDS, and to (2) investigate immunological mechanisms underlying the disease.